Franco Frattini, who served twice as Italy's foreign minister and held several other cabinet posts, died on Saturday at the age of 65, Italian media reported.
Frattini, who had been ill for some time with cancer, died in a Rome hospital.
He was foreign minister under governments headed by Prime Minister Silvio Berlusconi 2002-2004 and 2008-2011 and held two other cabinet posts in governments headed by Berlusconi and Lamberto Dini in the 1990s.
From 2004 to 2008 he was European commissioner for justice and at the time of his death he was president of Italy's Council of State, a consultative body that oversees public administration.
He started his political activity as a member of the Socialist Party and later joined Berlusconi's centre-right parties.